It is known that N-tritylimidazole derivatives show fungicide activities. For instance, U.S. Pat. No. 3,660,577 discloses antimycotics of the general formula (II), wherein R, R.sub.1 and R.sub.2 denote hydrogen, lower alkyl radicals and phenyl; X stands for alkyl groups or for electronegative substituents; and n denotes an integer from 0 to 2, and n may have different meanings in the individual benzene rings. ##STR3##
It is known that, in general, among the very many prducts embraced by general formula (II), mono-substituted ones are more active as antifungal agents than poly-substituted ones. Thus, for instance, FR 1.600.990 discloses antimycotics of general formula (III), where X stands for several substituents, halogens included. This document describes comparative tests of monosubstituted halogen derivatives versus analogous di- and tri-substituted ones; from the results it is clear that mono-substituted derivatives have higher antifungal activities. In fact, the most successful commercial product included in general formula (III) is the monosubstituted chloro derivative named Clotrimazole. ##STR4## U.S. Pat. No. 3,764,609 disclosed 1-(5H-dibenzo[a,d]cyclohepten-5-yl)-1H-imidazole derivatives of general formula (IV), wherein R.sub.1 and R.sub.2 are the same or different and each represents a hydrogen or halogen atom or a lower alkyl group, R.sub.3, R.sub.4 and R.sub.5 represent a hydrogen atom or an alkyl group, X represents a single bond, a --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH-- group or a group --CH.sub.2 --CHHal-- wherein Hal represents a chlorine or bromine atom. It is said that products of general formula (IV) possess fungicidal activity, although no data is given in this document. It is noteworthy that general formula (IV) does not embrace any product di-substituted in the same phenyl ring. Actually no di-substituted product is described in this document, even with substitution in different rings. Among the described products in this patent, the one which is structurally closest to those of the present invention is the product of formula (V), which has a bromine atom in position 3.
Squibb U.S. Pat. No. 4,420,474 discloses synergistic antifungal compositions of antimycotics and Azalomycin F. In its Table I 1-(3-chloro-10,11-dihydro-5H-dibenzo[a,d]dicyclohepten-5-yl)-1H-imidazole is mentioned with the company name SQ 80896, but without giving any indication for its preparation or use. To the best of our knowledge, SQ 80896 is structurally the closest product to the products of the present invention, ever described. In any case, the pharmacological data in Table I of U.S. Pat. No. 4,420,474 clearly show that SQ 80896 is considerably less active than Clotrimazole (according to MIC parameters against Candida alibicans).
Despite the usefulness of the already known commercial antifungal agents, research in this field is very intensive because some fungi species have become resistant to old compounds (particularly to the widespread Clotrimazole). This represents a serious problem, specially in hospitals and big towns. It is very important to search for new antifungals with powerful action and wide spectrum; but it is also important to provide new antifungals active against a limited number of fungal infections, some of which could be resistant to old products. Thus, new compounds (Econazole, Miconazole, . . . and notably Bifonazole) are being introduced in the market as soon as they show any antifungal activity against some species similar to, or higher than, the activity of old products, notably of Clotrimazole which is still the most active commercial product against some species.